Components of Participating OrganizationsThis FOA is developed as an
NIH Roadmap Initiative. All NIH Institutes and Centers participate in NIH
Roadmap Initiatives. This FOA will be administered by the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (http://www.niams.nih.gov) on behalf of the
NIH.

Purpose.The
National Institutes of Health invites research applications to develop,
test and evaluate new domains as per PROMIS item bank development
procedures and/or validate new or existing PROMIS item banks in various
clinical populations as part of the PROMIS Network.
The PROMIS Network is intended to be a resource for the clinical research
community.Successful
applicants will join a network of existing and new Centers to foster the
advancement, development, and application of new technologies for the use
of Patient Reported Outcomes in clinical research by working
collaboratively to achieve the goals of the NIH PROMIS initiative(http://nihroadmap.nih.gov/clinicalresearch/overview-dynamic
outcomes;www.nihpromis.org). This FOA is one of a group of four interrelated FOAs designed
to support the second phase of the NIH RM PROMIS
Initiative.

Mechanism
of Support. This FOA will utilize the U01 Research
Project--Cooperative Agreements grant
mechanism. It runs in parallel
with three (3) U54 RFAs with interrelated scientific scope: RFA-RM-08-022, RFA-RM-08-024, and RFA-RM-08-025.

Funds
Available and Anticipated Number of Awards.The total amount of funding from
the NIH Roadmap for new awards under this initiative is approximately
$5.65 million total costs per year for approximately 5-10 new awards in
FY09.

Budget and Project Period.Direct costs are
limited to $350,000 per year for a small domain site and $1,000,000 per
year for a large clinical site. The total project period for an
application submitted in response to this FOA may not exceed four (4)
years.

Eligible Project Directors/Principal Investigators
(PDs/PIs). Individuals with the
skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/organization to develop
an application for support. Individuals from underrepresented racial and
ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Number of PDs/PIs. More than
one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.

Number of Applications.Applicants may
submit more than one application, provided they are scientifically
distinct.

Resubmissions.Resubmission
applications are not permitted in response to this FOA.

Renewals. Renewal (type 2, formerly “competing
continuation”) applications will be accepted, as well as new (type 1)
applications.

The
Patient-Reported Outcomes Measurement Information System™ (PROMIS) is an NIH Roadmap (RM)-funded
initiative. The original FOA, “Dynamic Assessment of
Patient-Reported Chronic Disease Outcomes” (RFA-RM-04-011)
was awarded in August, 2004 to six primary research sites and a statistical
coordinating center to form the PROMIS Network. The broad objectives of
the initial FOA were to: 1) develop and test a large bank of items measuring
patient-reported outcomes (PROs), 2) create a computerized adaptive testing (CAT) system that would allow for efficient, psychometrically robust assessment of PROs in
clinical research involving a wide range of chronic diseases, and 3) create a
publicly available system that could be added to and modified periodically and
that would allow clinical researchers to access a common repository of items
and CAT system. For details on the original RFA, see http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-011.html.

The PROMIS Network met or exceeded its goals of
developing item banks of disease non-specific PRO domains and making them
available as short forms and CAT through the PROMIS Assessment Center. Documentation of the PROMIS Network and Assessment Center efforts is reported by
the grantees at www.nihpromis.org.
A summary of the mid-course evaluation conducted on June 19, 2007 is available
at: http://nihroadmap.nih.gov/clinicalresearch/promis/pdf/promismidcoursereview.pdf
Progress and plans from the first two years of the project are also available
in a supplement issue of Medical Care (Vol 45, No. 5, May, 2007, Suppl 1).
These achievements have set the stage for the next funding phase of
development.

Due to the success of PROMIS and the growing
interest of various research and health care sectors in this methodology, the
NIH Roadmap has authorized an additional four years of funding for this
initiative. This second funding phase is structured into four
interrelated FOAs that seek to address the scientific needs and priorities
identified during the mid-course review, as well as feedback from the original
PROMIS investigators, NIH Science Officers, and NIH Scientific Monitoring Board
(SMB).

The overall goals of the second funding phase
are to validate the PROMIS domains in the context of clinical studies and to
develop the PROMIS system to facilitate adoption by clinical researchers, consistent
with the overall goals of the program.

The objectives of the NIH RM PROMIS initiative
during the next four years include:

Conduct validation studies and evaluate usability of the
PROMIS domains and tools for clinical trials and other clinical research
settings,

Continue testing the items and item banks in different
chronic disease areas and ethnic groups to demonstrate their content validity,

Evaluate responsiveness to change to ensure the usefulness
of the items and instruments in clinical research,

Develop a fully-functional CAT system and scannable short
forms,

Develop additional domains,

Calibrate items translated into Spanish and other languages
and conduct concurrent validity testing,

Develop additional modes of administration,

Facilitate use by the clinical research community,

Build partnerships to secure long-term sustainability for
the PROMIS domains and tools.

An important priority during the second funding
phase of PROMIS will be domain development and validation focused on the
following populations:

Pediatrics

Women

Minorities

Persons with disabilities

Effort during the second funding phase of
PROMIS will be to emphasize representation of minorities, women, underserved
populations, and especially children in all PROMIS-related
research.

1) encourage
active planning and direction of the PROMIS Network’s scientific
activities and research priorities;

2) facilitate
coordination among PROMIS Network investigators and foster greater
opportunities for synergy within NIH and between other Federal agencies, health
care organizations and foundations and other interested stakeholders;

3) provide a
scientifically sound forum for the development and documentation of PROMIS
standards and guidelines and the advancement of PRO science; and

4) expand
existing and seek new partnerships and collaborations with private
organizations that will facilitate the transition to non-Roadmap funding
sources by the end of the project period in FY2012.

This FOA consists of the following four
interrelated FOAs that describe the short- and long-term goals for the second
funding phase of PROMIS and how this network will be structured and managed.
The PROMIS Network is defined as the consortium of investigators that lead the
different components of the PROMIS Network funded through these FOAs:

PROMIS Network
Center-PNC (RFA-RM-08-022):
The PNC will provide overall coordination, management, infrastructure and
leadership for the PROMIS Network, and planning and implementation of the
transition from the first to the second funding phase. The PNC will support and report to the PROMIS Network Steering Committee (PNSC), which will be
responsible for overseeing the scientific and administrative activities of
the network, consistent with the terms and conditions of the PROMIS awards
and applicable regulations. The PNC will develop, along with the rest of
the PROMIS Network, the strategic plan and research agenda to address NIH
RM PROMIS goals and priorities, and monitor data accrual to ensure PROMIS
is representative of the US general population with a particular emphasis
in research involving children, women, minorities, and those with
disabilities. The PNC will continue establishment of PROMIS
standards for domain development and clinical validation, planning and
development of collaborations, partnerships, and the successful transition
to a sustainable PROMIS funding structure by the end of this PROMIS
project period in FY2012.

PROMIS Statistical
Center-PSC (RFA-RM-08-025):
The PSC will coordinate the data collection from the domain research
sites, manage data quality, assist in general population sampling for new
item bank testing, and provide psychometric and statistical support for
the network as well as development of PROMIS-approved translations of new
and extant domains.

PROMIS Technology
Center-PTC (RFA-RM-08-024):
The PTC will develop and provide computer administration services,
including CAT, web access to short forms, and other administration
modalities of the PROMIS item banks in clinical research. The PTC will support the CAT and informatics needs of the network. In addition, the PTC may provide these services to the greater research community at a minimum cost.

PROMIS Research
Sites-PRS (RFA-RM-08-023)
(this announcement): The PRS will develop, test and evaluate new domains
as per PROMIS item bank development procedures and/or validate new or
existing PROMIS item banks in various clinical populations.

It is expected that PROMIS (www.nihpromis.org)
will continue to expand and improve the science of PRO assessment, while at the
same time making the products of this work widely available and acceptable to
interested stakeholders. The increased efficiency, flexibility, and
sensitivity of the PROMIS tools will allow greater compatibility between
studies and greater statistical power with reduced patient reporting burden.
Ultimately, PROMIS will need to become a self-sustaining research resource
adaptable to future research needs. Therefore, establishing a functional
public-private partnership (PPP) is intended to be an essential component of
this second funding phase of PROMIS.

2.
Research Objectives

The PROMIS network developed a domain framework
and initially selected five primary domains for item bank development: 1)
physical functioning, 2) pain-behavior impact, 3) fatigue, 4) emotional
distress, and 5) social role participation based upon the broader self-reported
constructs of physical, mental and social health. A literature review of
extant items, supplemented with new items, was used as the basis for generating
the initial item pools which were then subjected to psychometric validation
including qualitative item review (QIR) employing focus groups and cognitive
testing to refine the items, improve understandability, and ensure adequate
saturation of the domain area. The resulting item pools were then evaluated
in large general population and clinical samples. After assessing
unidimensionality, item fit, differential item functioning (DIF) and other
psychometric properties, the resulting item banks were IRT calibrated to form a
common metric in order to administer tailored short forms or CATs.
Reports on the initial network efforts are available in a special issue of
Medical Care (May 2007, Vol. 45, Suppl. 1), and
documentation of network procedures and results are available at www.nihpromis.org.
These domain validation efforts are collectively described as ‘wave
1’ activities in all PROMIS-related publications or the website noted
above.

To date, PROMIS has developed version 1.0 item banks of a
core set of generic PROs including: 1) pain impact and behavior; 2) physical
function; 3) fatigue; 4) emotional distress (anxiety, depression, anger) and 5)
social role functioning. These item banks were derived from study
participants in the general population as well as those with a wide range of
chronic diseases representing a range of demographic characteristics.
Additional PROMIS supplemental efforts have developed item banks for sleep-wake
functioning, sexual functioning, perceived cognitive functioning, and (positive
and negative) illness impact. All of these domains should be considered
for further validation testing in specific disease groups (see Clinical
Validation Studies below) during the second funding phase of PROMIS.
During Wave 1 testing, preliminary validity studies were conducted to assess
the concurrent validity of the PROMIS item banks to legacy scales. In addition,
the PROMIS network has initiated early validation studies in specific clinical
populations such as low back pain, major depression, rheumatoid arthritis,
chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) to
compare selected PROMIS item banks to other domain and disease measures, and to
assess sensitivity to change of the PROMIS item banks. The current network
is also conducting a mode of administration study to determine the relationship
of these item banks administered in various modes. These are referred to
as ‘Wave 2’ protocols as they were not described in the original
FOA (see Wave 2 studies; www.nihpromis.org). These initial
validation trials will not be completed by the deadline for applications to
this FOA, so it is expected that the PROMIS Network Center (PNC; RFA-RM-08-022)
will coordinate the efforts of the second funding phase of PROMIS Research
Sites to address any additional validity questions generated from the results
of these initial PROMIS Wave 2 validity trials.

With the second funding phase of PROMIS, we therefore, seek
to: 1) develop new domains and item banks in multiple languages to facilitate
international trials and 2) conduct clinical validation studies in a variety of
patient populations (see Clinical Validation Studies below) consistent with the
goals of the program. Based on recommendations from the PROMIS Scientific
Monitoring Board (SMB) and the PROMIS mid-course review, the second funding
phase of PROMIS Research Sites are strongly encouraged to consider including
child and adolescent cohorts, women, minorities, and underserved populations in
item testing or validation samples.

The objective of this FOA is to solicit applications for
PROMIS Research Sites (PRS). These sites will work collaboratively with
investigators in the PROMIS Network, the PSC, the PNC, the PTC and NIH staff. Among the goals of the PRS are: 1) conducting further development and IRT testing to psychometrically evaluate and validate new item banks and domains according to
PROMIS standards established by the PNC (RFA-RM-08-022)
based on the work performed by the original PROMIS network, 2) validate new
and/or existing domains in clinically meaningful contexts by conducting trials
(see Clinical Validation Studies-below). The PRS may propose to develop new
domains with or without subsequent early clinical validation studies, or they
may propose to conduct clinical validation trials that include existing or newly
developed PROMIS domains without developing domains

These new and extant PROMIS domains will be useful across a
broad range of clinical research and practice to assess response to
interventions and inform modification of clinical treatment plans. To achieve
this goal, domain development and clinical testing and validation will
ultimately need to meet or exceed the domain development and psychometric rigor
established by the original PROMIS network with clear and transparent standards
for item development, testing, and validation coordinated by the PNC (RFA-RM-08-022)
that will ensure widespread acceptance and understanding of the PROMIS tools to
all interested stakeholders including the Food and Drug Administration-FDA (http://www.fda.gov/cder/guidance/5460dft.pdf)
and its European counterpart, the European Medicines Agency-EMEA (http://www.emea.europa.eu/

Domain Development

The PRS will propose, design and assess preliminary
validity of new domains employing activities such as QIR, cognitive testing,
assessment of dimensionality and DIF as described above for existing PROMIS
domains developed as ‘Wave 1’ activities and eventually to
standards established by the PNC (RFA-RM-08-022).
These new domains should seek to fill existing gaps in the current domain
architecture (www.nihpromis.org)
and create an expanding family of PROMIS-studied and approved
domains. These studies should also strive to evaluate novel
technologies and approaches to expand the usefulness of PRO assessments
whenever appropriate and possible. For example, there is a growing
awareness that collecting symptom data directly from patients using PRO tools
can improve the accuracy and efficiency of symptomatic adverse experience data
collection. As a result, there is increasing attention among investigators,
regulatory agencies, and pharmaceutical sponsors to incorporating self-reports
when documenting adverse experiences.

Domain validation should seek to address populations often
under-represented in clinical studies especially including women, children,
minorities and those with disabilities. Populations proposed for
development and testing of these new domains should be fully representative of
the population likely to be studied with this domain. An important goal of
these validation efforts is to develop useful outcome indices that will be
adopted for a wide range of clinical
trials.

All data collection and analyses for these studies will be
coordinated with the PSC (RFA-RM-08-025)
and the PTC (RFA-RM-08-024)
as part of the larger PROMIS network.

Examples of new domains include, but are not limited to:

pediatric versions of existing domains

substance abuse

GI distress

adverse experiences of treatments on symptoms,
functioning or other aspects of quality of life

satisfaction with care

physical and/or mental health satisfaction

positive psychological functioning

social health satisfaction

stress

The research opportunities created by PROMIS and by the
current understanding of PROs exceed the available funding from NIH Roadmap.
Therefore, it is expected that applicants that do not obtain funding under the
second funding phase of PROMIS will submit their proposals to the most relevant
NIH institute or center for funding consideration. Although these and other
domain development efforts will formally be outside of the PROMIS network,
applicants will be encouraged to propose collaborations with the PROMIS network
via the PNC (RFA-RM-08-022)
and work closely with the PSC (RFA-RM-08-025)
and coordinate efforts with the overall second funding phase of the PROMIS
Network. Consistent with the purposes of the NIH Roadmap effort, the
PROMIS second funding phase priority will be for the development and
testing of new domains that address outcome variables of interest across a
broad range of diseases and clinical trials as opposed to disease-specific
domains. Also, since not all new PRO domain development will be amenable
to IRT modeling, all proposed developments need to address how they can be
incorporated into the PROMIS family of domains.

Clinical Validation Studies

The PRS will propose and implement new clinical validation
studies of varying size and scope. Principal investigators that propose
to conduct clinical validation studies in association with development of new
domains would likely conduct such trials in a clinically well defined, enriched
population. On the other hand, PRS could propose large scale validation
studies in the context of NIH phase III clinical trials intended to change
patient care. For example, PROMIS domains could be utilized as parallel
primary or secondary endpoints in these clinical trials along with other
measures of the same construct to study concurrent validity and compare to
legacy scales and/or their relationships to physical health indices.

An important focus of these PROMIS second funding phase
clinical trials will be to address issues of validity (e.g. face, content, construct),
precision, and responsiveness (sensitivity to change) including minimally
important differences of these newly developed domains and comparing to legacy
scales. These are important characteristics of outcome measurements as
described by the OMERACT filter (www.omeract.org) and the Medical Outcomes
Trust Scientific Advisory Committee’s recommendation for assessing health
status and quality-of-life instruments (Quality of Life Research 2002, 11;
193-205). Each domain will have addressed these same issues during psychometric
development. Goals of domain validation may vary as the needs of clinical
investigators may vary from those of clinical researchers. Since
validation of a PRO is ultimately a process, and not an endpoint of itself,
proposed clinical trials should also seek to expand upon the initial validation
studies of domains that have been conducted as part of the original PROMIS
efforts. These trials need to be conducted to achieve standards that are statistically and
clinically defensible as noted above. The PRS clinical validation studies
should be proposed in patients with a variety of diseases, especially those not
well represented in “Wave 1” studies with attention to those patients
in underrepresented populations such as women, children, minorities, and those
with disabilities. In addition, proposed PRS trials should evaluate new
technologies whenever possible.

The nature of these proposed validation trials
can vary from large to small, depending on the goals of the trial and how it is
envisioned the study would contribute to the overall long-term validation
process. For example, large trials could be proposed to study and
validate a domain in a population that would add substantially to the
generalizability of the domain to the general US population. On the other
hand, small trials in enriched clinical samples could be proposed that compare
the PROMIS item banks to clinical “gold standard” measures of the
construct that may be difficult to obtain in large trials or to study/validate
item banks in special populations. Both types of trial may address
proof-of-concept issues, especially for early domain validation efforts and
should help provide a sufficient base of validity data for adoption into
clinical trials and/or as the basis of support for further hypothesis testing
of the domain of interest.

In addition to clearly stated and described
goals and objectives, applications should explore alternate strategies for
interpretation of outcomes such as responder analyses or area under the curve
versus landmark approaches to maximize endpoint interpretation, comparability
to other studies that employ the same PROMIS domains and adaptability to
varying clinical situations and settings. Applications should also
explore the adaptability of PROMIS domains as substitutes for part of a
composite index, or as a sufficient stand-alone outcome measure, for currently
accepted and widely employed endpoints. The PRS proposed clinical trials
may also explore approaches to combine subjective (PRO) and objective (genetic
abnormality-SNP) information. It should be the intent to study as many
PROMIS domains as possible in as many different diseases as possible especially
with sensitivity to change data.

Sites doing primary clinical validation studies
are expected to conduct data collection and analyses both on their own, and in
collaboration with the PSC (RFA-RM-08-025).

As mentioned above, the research opportunities
created by PROMIS and by the current understanding of PROs exceed the available
funding from NIH Roadmap. Therefore, regarding clinical trial possibilities,
those proposals that do not receive funding for the second funding phase of
PROMIS could subsequently be considered for additional R01-NIH
institute-specific or supplemental funding. Such studies could be disease
or condition-specific and of special interest to particular NIH institutes or
centers with their respective funding mechanisms. Examples of such
possibilities include the additional PROMIS-initiated studies in pediatrics
(parent-proxy), those that are addressing the unique needs of patients with
disabilities, as well as domain validation in patients with fibromyalgia.
Explicit policies for how these additional funded studies will ultimately be
incorporated in PROMIS will be established by the PNC (RFA-RM-08-022).

For example, because PROMIS needs to be
self-sustaining and applicable to as wide a portion of the population as
possible, additional and associated research validation studies should be
proposed. Professional organizations could consider studies using instruments
developed in the second funding phase of PROMIS as components in hospital or
clinical health maintenance organization (HMO) practice settings.
Insurance companies, and other Federal agencies such as the VA or CMS, could consider scientifically rigorous observational studies with domains developed in the
second funding phase of PROMIS to evaluate effectiveness of health care
delivery and contribute to ongoing validation efforts. For any such
proposed trials, the relationship between the parent domain validation and
standardization process needs to be addressed. Similarly, collaborations
(extant and new) with the regulated industry could be expanded and could
include efforts to incorporate domains developed in the second funding phase of
PROMIS as endpoints in clinical trials intended to support product registration
or label claims, or to support translation and validation of items for
international clinical trials and cross cultural research.

Organizational Structure of the PROMIS
Network and Network Center

Refer to Organizational Structure of the
PROMIS Network and Network Center as described in RFA-RM-08-022, The PROMIS
Network Center in Part II, Section I, 2. Research Objectives

Governanceof the PROMIS Network

As part of the cooperative PROMIS network,
the PRS will participate in the following governance structure. See: Organizational
Structure of the PROMIS Network and Network Center as described above.

1. The PROMIS Network
Executive Committee (PNEC), consisting of the Chair, elected by the PNSC, the
NIH Chief Science Officer (CSO), one or more additional NIH Science Officers
appointed by the NIH Project Officer, and one or more Principal Investigator(s)
selected by the PNSC will provide scientific management, leadership, and
overall governance of the operations of the PROMIS Network.

2. The PNSC will
function as the main governing board of all projects awarded under these RFAs,
as well as projects that transition from the first to the second PROMIS funding
phase. The PNSC will be the primary mechanism for NIH interactions and
collaboration with the awardees and with the PROMIS Network. The voting
membership of the PNSC will consist only of the NIH Science Officers and
Principal Investigators (PIs) of each cooperative agreement award.
Face-to-face meetings of this committee will occur at least four times per
year. Other NIH staff may attend PNSC meetings when their expertise is required
for specific discussions.

3. The PNC (RFA-RM-08-022)
will coordinate and direct all activities of the PROMIS Network including those
of the PSC (RFA-RM-08-025),
the PTC (RFA-RM-08-024)
and the PRS (RFA-RM-08-023). These groups will be interactive and
collaborative with each other as well as the NIH, the PNSC, and Scientific
Monitoring Board as described below.

4. The NIH Science Officers
(SOs), program officials from NIH institutes involved with specific awards and
FOAs, will have substantial scientific and programmatic involvement with the
conduct of these awards, through technical assistance, advice, and
coordination, above and beyond normal program stewardship for grants. The
SOs will work in partnership with the PIs, and will provide significant input
in the planning and conduct of the research, in areas such as item selection
for testing, testing methodologies, data analysis planning, data interpretation
and, if appropriate, co-authoring manuscripts for publication. The SOs
will also serve as scientific liaisons between the awardees and other NIH
program staff; they will have the option to recommend re-allocating NIH support
among awardees as scientific goals evolve.

5. The NIH Project
Officer (PO) will have responsibility for normal program oversight and
stewardship of the award. The PO will serve as a non-voting member of the
PNSC, conduct continuous review of all activities to ensure objectives are
being achieved, and have the option to recommend withholding support to an
awardees’ institution if technical performance requirements are not met,
as appropriate.

6. The Scientific
Monitoring Board (SMB) will evaluate the awardees’ progress in relation
to the goals of this initiative. The SMB will consist of approximately six
scientists who are not affiliated with any of the awardees’ institutions.
The SMB members will be selected for their broad expertise in relevant topics
to include methodologists (Information Technology-IT, psychometrics, cognitive
testing), clinical metrologists, and members of the Federal government (e.g.
FDA, VA, CMS, AHRQ). The SMB members will evaluate awardee efforts to ensure
adequate communication and sharing. They will make recommendations
regarding coordination of these activities and related, future projects. They
may also participate in PNSC conference calls. Members of the SMB may attend
face-to-face PNSC meetings on a rotating basis to provide input and feedback to
those not in attendance.

7. The PNSC, along with
the SMB and the PNC, will be involved in discussions and decisions regarding
initial transition from the first to the second PROMIS funding phase and final
transition plans after Roadmap support.

This
funding opportunity will use theNIH Research Project--Cooperative Agreements (U01)award mechanism(s).The Project Director/Principal Investigator (PD/PI)
will be solely responsible for planning, directing, and executing the proposed
project.

This funding opportunity
will use a cooperative agreement award mechanism. In
the cooperative agreement mechanism, the Project Director/Principal
Investigator (PD/PI) retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the Section VI. 2. Administrative
Requirements, "Cooperative Agreement Terms and Conditions of
Award".

At this time, the NIH does not
intend to continue this project beyond this four-year funding period (FY2009
– FY2012). A fundamental objective of the NIH Roadmap (RM) for
PROMIS has been to develop new methodologies to evaluate Patient Reported
Outcomes (PROs) as part of the RM efforts in re-engineering the clinical
research enterprise. The role of the NIH Roadmap in this effort has been
to provide the “incubator space” for this major initiative to
develop and mature, and it has been appropriate, therefore, to provide the initial
funding for the growth of PROs capability through the Common Fund from which
Roadmap projects have been supported.

NIH is committed to ensuring that the Federal
investment in the development of PROMIS will result in improvements in clinical
trial methodologies and ultimately improvements in public health. NIH
would like to be engaged in an ongoing Public-Private Partnership (PPP) in
order to ensure that the NIH stewardship of the public health trust related to
patient-reported outcome (PRO) measures continues beyond the scope of the
current solicitation. One means to accomplish that end is via the
formation of a PPP. PPPs can be initiated by NIH and/or awardee
institutions. NIH has the following goals with respect to the development of a
PPP:

a) To ensure the
exceptional scientific quality of the research and maintain the clinical
relevance of the PROMIS work;

b) To ensure that broad
interest continues to drive the PROMIS activity through a representative
governance structure including communities such as NIH, other Federal agencies,
academia, clinicians, industry, and patient groups;

c) To leverage the NIH
Roadmap investment in PROMIS both during and beyond the second funding phase
with additional support and resources from other sectors; and

d) To ensure that all
PROMIS resources remain widely accessible and at minimal cost to advance
clinical research and practice.

2. Funds Available

The NIH Roadmap intends to commit
approximately $5.65 million in FY2009 to fund 5-10 new and/or competing renewal grant applications
in response to this FOA. The earliest anticipated start
date for awards under this funding opportunity is September 1, 2009.

PRS applicants for small domain sites may
request up to $350,000 direct costs annually; PRS applicants for large clinical
sites may request up to $1 million direct costs annually. The total
project period for an application submitted in response to this FOA may not
exceed four (4) years.

The estimated amount of funds available for support of5-10 projects awarded as a
result of this announcement is $5.6
million for fiscal year 20 09. Future year amounts will depend on annual
appropriations.

Because the nature
and scope of the proposed research will vary from application to application,
it is anticipated that the size and duration of each award will also vary.
Although the financial plans of the IC(s) provide support for this program,
awards pursuant to this funding opportunity are contingent upon the
availability of funds and the receipt of a sufficient number of meritorious
applications.

Facilities and
administrative costs requested by consortium participants are not included in
the direct cost limitation, see NOT-OD-05-004.

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility
of the investigators and applicant organizations, and should be determined by
the scientific goals of the project. Applications for grants with multiple
PDs/PIs will require additional information, as outlined in the instructions
below. The NIH review criteria for approach, investigators, and environment
have been modified to accommodate applications involving either a single PD/PI
or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that
the structure and governance of the PD/PI leadership team as well as the
knowledge, skills and experience of the individual PDs/PIs will be factored
into the assessment of the overall scientific merit of the application.
Multiple PDs/PIs on a project share the authority and responsibility for
leading and directing the project, intellectually and logistically. Each
PD/PI is responsible and accountable to the grantee organization, or, as
appropriate, to a collaborating organization, for the proper conduct of the
project or program, including the submission of required reports. For further
information on multiple PDs/PIs, please seehttp://grants.nih.gov/grants/multi_pi.

Applicants
are not permitted to submit a resubmission application in response to this
FOA.

Renewal (type 2,
formerly “competing continuation”) applications will be accepted,
as well as new (type 1) applications.

Institutions are not
limited in the number of applications that may be submitted in response to any
of the four interrelated FOAs of this FOA: RFA-RM-08-022 (U54), RFA-RM-08-023 (U01), RFA-RM-08-024 (U54), or RFA-RM-08-025 (U54). If an institution applies for more than one
U54, the applicant needs to give careful consideration to the different scope
of each of the U54s and the value of diversity of scientific leadership and
project teams to each application in optimally achieving the overall goals of
the program, as well as ensuring that adequate and consistent commitment levels
can be met for any of the projects for which an applicant might apply.

Applicants may submit more
than one application, provided each application is scientifically distinct.

Each PD/PI is expected to commit 3.0 person months or
more effort to ensure success of the program

Applications may be submitted from single
institutions or consortia of institutions.

Applications must be
prepared using the most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866)
705-5711 or through the web site at http://www.dnb.com/us/.
The D&B number should be entered on line 11 of the face page of the PHS 398
form.

The title and
number of this funding opportunity must be typed in item (box) 2 only of the
face page of the application form and the YES box must be checked.

SPECIAL INSTRUCTIONS

Applications
with Multiple PDs/PIs

When multiple PD/PIs are
proposed, use the Face Page-Continued page to provide items 3a – 3h for
all PD/PIs. NIH requires one PD/PI be designated as the “contact
PD/PI” for all communications between the PD/PIs and the agency. The
contact PD/PI must meet all eligibility requirements for PD/PI status in the
same way as other PD/PIs, but has no special roles or responsibilities within
the project team beyond those mentioned above. The contact PD/PI may be changed
during the project period. The contact PD/PI should be listed in block 3 of
Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page
1-Continued. When inserting the name of the PD/PI in the header of each
application page, use the name of the “Contact PD/PI, et. al.” The
contact PD/PI must be from the applicant organization if PD/PIs are from more
than one institution.

All individuals designated
as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI
role in that system (other roles such as SO or IAR will not give the PD/PI the
appropriate access to the application records). Each PD/PI must include their
respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing
Multiple PDs/PIs will be required to include a new section describing the
leadership plan approach for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled “Multiple PD/PI Leadership
Plan” must be included. A rationale for choosing a multiple PD/PI
approach should be described. The governance and organizational structure of
the leadership team and the research project should be described, and should
include communication plans, process for making decisions on scientific
direction, and procedures for resolving conflicts. The roles and
administrative, technical, and scientific responsibilities for the project or
program should be delineated for the PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award.

The requests from federal agencies, including
the NIH intramural program, will not include any salary and related fringe
benefits for career, career conditional or other federal employees (civilian or
uniformed service) with permanent appointments under existing position ceilings
or any costs related to administrative or facilities support (equivalent to
Facilities and Administrative costs).

In general, the budget requests will be
limited to the incremental costs required for carrying out the proposed
work. These costs may include salary for staff to be specifically hired
under a temporary appointment for the project, consultant costs, equipment,
supplies, travel, and other items typically listed under Other Expenses. While
support for extramural collaborators may be requested in a separate grant
application, funds can be requested for services by an external investigator or
contractor as a subcontract/consortium including the applicable indirect
(F&A costs) of the contractor/collaborating institution.

Justification must be provided for all
requested support and for the Federal employees who will be committed to the
project although no funds are requested in the application.

Applicants should
indicate the number of person-months devoted to the project, even if no funds
are requested for salary and fringe benefits.

3.
Submission Dates and Times

Applications must be
received on or before the receipt date described below (Section
IV.3.A). Submission times N/A.

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research

Name, address, and telephone number of
the Principal Investigator

Names of other key personnel

Participating institutions

Number and title of this funding
opportunity

Although a letter of
intent is not required, is not binding, and does not enter into the review of a
subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.

Applications must be
prepared using the forms found in the PHS 398 instructions for preparing a
research grant application. Submit a signed, typewritten original of the
application, including the checklist, and three signed photocopies in one package to:

Applications must be received on or before the
application receipt date) described above (Section
IV.3.A.). If an application is received after that date, the application
may be delayed in the review process or not reviewed. Upon receipt,
applications will be evaluated for completeness by the CSR and for responsiveness
by the reviewing Institute Incomplete and/or non-responsive applications will
not be reviewed.

The NIH will not
accept any application in response to this funding opportunity that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an Introduction describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards
are subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement. The Grants Policy Statement can
be found at NIH Grants
Policy Statement.

Pre-award costs
are allowable. A grantee may, at its own risk and without NIH prior approval,
incur obligations and expenditures to cover costs up to 90 days before the
beginning date of the initial budget period of a new or renewalaward if such costs: 1) are
necessary to conduct the project, and 2) would be allowable under the grant, if
awarded, without NIH prior approval. If specific expenditures would otherwise
require prior approval, the grantee must obtain NIH approval before incurring
the cost. NIH prior approval is required for any costs to be incurred more than
90 days before the beginning date of the initial budget period of a new or
renewal award.

The incurrence
of pre-award costs in anticipation of a competing or non-competing award
imposes no obligation on NIH either to make the award or to increase the amount
of the approved budget if an award is made for less than the amount anticipated
and is inadequate to cover the pre-award costs incurred. NIH expects the
grantee to be fully aware that pre-award costs result in borrowing against
future support and that such borrowing must not impair the grantee's ability to
accomplish the project objectives in the approved time frame or in any way
adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements and Information

Annual Meetings

PROMIS Research Site Principal Investigators will
coordinate and collaborate on the formation of a Steering Committee that will
meet for a total of four (4) meetings annually. Three (3) of the Steering
Committee meetings will be held in the Bethesda, MD area and one (1) will be
held at a different Research Site each year. Applicants should include
travel and costs associated with participating in those meetings in the
budget.

Letters of Support

Include a letter documenting institutional commitment to the
PROMIS Network, including provision of funding, space, faculty positions,
and/or commitments for construction or renovation. A letter from an
appropriate institutional official, generally a dean or provost, should follow
the Research Plan. If multiple institutions are involved in the center
application, a letter should come from each institution.

Awardees must agree to the "Cooperative Agreement Terms
and Conditions of Award" in Section VI.2.A "Award Administration
Information".

Research
Plan Page Limitations

All applications and proposals for NIH funding must be
self-contained within specified page limitations. The page limit for
the PROMIS Network Center research plan (including overview, and specific aims,
background, and significance, preliminary studies, and research design and
methods) is 25 pages. Please refer to the
format described above in Section IV, 1 and 6.

Do
not use the Appendix to circumvent the page limitations of the Research Plan
component. An application that does not observe the required page limitations
may be delayed in the review process.

Resource Sharing
Plan(s)

NIH considers the sharing
of unique research resources developed through NIH-sponsored research an
important means to enhance the value of, and advance research. When resources
have been developed with NIH funds and the associated research findings
published or provided to NIH, it is important that they be made readily
available for research purposes to qualified individuals within the scientific
community. If the final data/resources are not
amenable to sharing, this must be explained in Resource Sharing section of the
application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm. The adequacy of the applicant’s data/resource sharing statements
will be considered by the NIH officials when making funding decisions.

During the first funding
phase, the PROMIS Network Steering Committee developed guidelines and
agreements on data sharing applicable to achieving the goals of the PROMIS
Roadmap (RM) Initiative (http://nihroadmap.nih.gov/clinicalresearch/overview-dynamicoutcomes.aspd). During the second funding phase, the NIH expects that the existing guidelines
will be reviewed, updated, and adopted by all collaborating institutions.
Consistent with such guidelines, NIH believes that the PROMIS goals will be
achieved only if all data generated by the PROMIS Network is deposited into the www.nihpromis.org website or another
NIH-approved common public database upon data verification. For this, the term
“data” is intended to include, but should not be limited to,
procedures, protocols and/or links to published procedures implemented in the
first funding phase of PROMIS; performance data for procedures and items and
item banks; primary data generated by domain and validation sites, and links to
published or unpublished manuscripts.

The reasonableness of any
data sharing plan or the rationale for not sharing research data will be
assessed by the reviewers. However, reviewers will not factor the proposed data
sharing plan or rationale into the determination of scientific merit or the
priority score.

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications where the development of
model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources, or state appropriate reasons why such sharing
is restricted or not possible. See Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless
of the amount requested, applicants seeking funding for a genome-wide
association study are expected to provide a plan for submission of GWAS data to the NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A
genome-wide association study is defined as any study of genetic variation
across the entire genome that is designed to identify genetic associations with
observable traits (such as blood pressure or weight) or the presence or absence
of a disease or condition. For further information see Policy for Sharing
of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH
Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

(d) Software
Development: Applications are expected to include a statement regarding how or
whether software developed through PROMIS funding will be depositedin the
PROMIS website (www.nihpromis.org) or another NIH-approved common public
database for public distribution, and how the applicant’s disposition of
software that it develops will advance the Research Objectives. The applicant
is also expected to include a statement regarding its planned response if the
PNSC recommends that a particular software application should be made available
for public use and maintained in a user-friendly format.

NIH has the following
goals with respect to software developed under these awards; the applicant
should address each of these goals in the statement described above.

1. The
software should be freely available to biomedical researchers, educators, and
institutions in the non-profit sector, such as institutions of education,
research institutions, and government laboratories.

2. The terms
of software availability should permit the commercialization of enhanced or
customized versions of the software, or incorporation of the software or pieces
of it into other software packages.

3. The terms
of software availability should include the ability of research institutions outside
the Center to modify the source code and to share modifications with other
colleagues as well as with the Center.

Management of Intellectual Property

Certain research plans will require collaboration and
coordination between investigators at different institutions, some of whom may
not be NIH funding recipients and who may have pre-existing intellectual
property obligations to third parties. It is understood that some information
developed under the grants will be proprietary and might not be shared
immediately without damaging the commercialization potential of the technology.
In addition, it is anticipated that commercial embodiments of the results of
such research may incorporate single inventions shared by several institutions,
or multiple inventions each from a separate institution. Therefore, grant
applicants are expected to address, for example, how the applicant will
coordinate patent prosecution and licensing activities, if necessary to enable
a licensee to access the bundle of intellectual property needed to take a
product to market on commercially viable terms consistent with achieving the
goals of the program. Suggested strategies include: (1) assigning intellectual
property rights to related inventions to an invention management firm; (2)
designating one organization to take the lead on patenting and licensing
related inventions; and (3) agreeing in advance that if multiple parties are to
independently license-related inventions, the total of stacked royalties will
not exceed a predetermined percentage rate. Alternatives to the suggested
strategies, which accomplish the same goals, will be considered. The
applicant's institution should avoid exclusively licensing those inventions
that are research tools unless either: (1) the field of use of the exclusive
license is restricted to commercial use; or (2) the exclusive licensee will
make the research tool available on reasonable terms. Applicants are directed
to the NIH policy on the dissemination of biological research resources
(“research tools”) at http://grants.nih.gov/grants/intell-property_64FR72090.pdf.

Applicants should note that the IP statements submitted
with the applications will be used following awards by the PNC to develop
Network-wide IP guidelines for collaborative activities. Applicants are
expected to include a statement in the applications indicating their
willingness to abide by the PNC IP guidelines approved by the PNSC and NIH, to
the extent they are consistent with the goals of the program, the
applicant’s IP management statement, and applicable grant regulations.

Section
V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review
criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are
complete and
responsive to the FOA will be evaluated for scientific and
technical merit by an appropriate peer review group convened by CSRand in accordance with NIH
peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.

As part of the scientific peer
review, all applications will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned a priority
score.

Receive
a written critique.

Receive
a second level of review by the appropriate national advisory
council.

The
following will be considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by peer review

Availability
of funds

Relevance
of the proposed project to program priorities

The potential for productive collaborations among PROMIS
investigators

Relevance to NIH Roadmap PROMIS priorities.

Adequacy
of resource sharing and IP management statements.

The
goals of NIH supported research are to advance our understanding of biological
systems, to improve the control of disease, and to enhance health. In their
written critiques, reviewers will be asked to comment on each of the following
criteria in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, weighting them as
appropriate for each application. Note that an application does not need to be
strong in all categories to be judged likely to have major scientific impact
and thus deserve a meritorious priority score. For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.

Significance:Does this study
address an important problem? If the aims of the application are achieved, how
will scientific knowledge or clinical practice be advanced? What will be the
effect of these studies on the concepts, methods, technologies, treatments,
services, or preventative interventions that drive this field?

Approach:Are the conceptual or clinical framework, design,
methods, and analyses adequately developed, well integrated, well reasoned, and
appropriate to the aims of the project? Does the applicant acknowledge
potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the
leadership approach, including the designated roles and responsibilities,
governance, and organizational structure, consistent with and justified by the
aims of the project and the expertise of each of the PDs/PIs? What is the importance of the PROMIS
Research Site research objectives to the PROMIS Network goals? Is it likely
that these research objectives will be completed within the project
period? Are the experimental design and methods adequate to achieve the
research objectives, including the involvement of basic and clinical
scientists, psychometricians, statisticians, and study design experts and
project managers in the conception, design, and proposed implementation of the
project? Are the proposed project milestones and the feasibility of achieving
the research objectives, adequate?

Innovation: Is the project original and innovative? For
example: Does the project challenge existing paradigms or clinical practice;
address an innovative hypothesis or critical barrier to progress in the field?
Does the project develop or employ novel concepts, approaches, methodologies,
tools, or technologies for this area?

Investigators:Are the
PD/PI(s) and other key personnel appropriately trained and well suited to carry
out this work? Is the work proposed appropriate to the experience level of the
principal investigator and other researchers? Does the PD/PI(s) and
investigative team bring complementary and integrated expertise to the project
(if applicable)?Are the qualifications of the basic and clinical investigators,
psychometricians, statisticians, and other design experts to conduct the
proposed research, and the appropriateness of the time commitments of each
investigator, adequate to the conduct to the project? Are there
adequate plans for ensuring effective communication, interaction, and
coordination among the PI(s), PROMIS Network, PROMIS Statistical Center, Research Sites and NIH staff? b) Do the applicants state their willingness to
collaborate extensively and share information, data, software and other
resources fully, consistent with meeting the goals of the program and with the
applicant’s submitted statements and applicable grant regulations?

Environment: Do(es)
the scientific environment(s) in which the work will be done contribute to the
probability of success? Do the proposed studies benefit from unique features of
the scientific environment, or subject populations, or employ useful collaborative
arrangements? Is there evidence of institutional support? Is the scientific environment in which the domain
research work will be done, and the unique features, if any, of the environment
adequate to support the proposed work?

2.A.
Additional Review Criteria:

In addition to the
above criteria, the following items will continue to be considered in the
determination of scientific merit and the rating:

Protection of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed (see the Research Plan section on Human
Subjects in the PHS 398 instructions).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to
include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated (see the Research Plan section on Human Subjects in the
PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to
be used in the project, the five points described in the Vertebrate Animals
section of the Research Plan will be assessed.

Biohazards: If materials or procedures are proposed that are
potentially hazardous to research personnel and/or the environment, determine
if the proposed protection is adequate.

2.B. Additional Review
Considerations

Budget: The reasonableness of the
proposed budget and the requested period of support in relation to the proposed
research. The priority score should not be affected by the evaluation of the
budget.

2.C.
Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment
on the reasonableness of the following Resource Sharing Plans, or the rationale
for not sharing the following types of resources. However, reviewers will not
factor the proposed resource sharing plan(s) into the determination of scientific
merit or priority score, unless noted otherwise in the FOA. Program staff
within the IC will be responsible for monitoring the resource sharing.

A
formal notification in the form of a Notice of Award (NoA) will be
provided to the applicant organization. The NoA signed by the grants management
officer is the authorizing document. Once all administrative and programmatic
issues have been resolved, the NoA will be generated via email notification
from the awarding component to the grantee business official (designated in
item 12 on the Application Face Page). If a grantee is not email enabled, a
hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Also Section
IV.5. Funding Restrictions.

The
following Terms and Conditions will be incorporated into the award statement
and will be provided to the Principal Investigator as well as to the
appropriate institutional official, at the time of award.

2.A.
Cooperative Agreement Terms and Conditions of Award

The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts
74 and 92 (Part 92 is applicable when State and local Governments are eligible
to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and
funding instrument used for this program will be the cooperative agreement an
"assistance" mechanism (rather than an "acquisition"
mechanism), in which substantial NIH programmatic involvement with the awardees
is anticipated during the performance of the activities. Under the cooperative
agreement, the NIH purpose is to support and stimulate the recipients'
activities by involvement in and otherwise working jointly with the award
recipients in a partnership role; it is not to assume direction, prime
responsibility, or a dominant role in the activities. Consistent with this
concept, the dominant role and prime responsibility resides with the awardees
for the project as a whole, although specific tasks and activities may be
shared among the awardees and the NIH as defined below.

2.
A.1. Principal Investigator Rights and Responsibilities

The Principal
Investigator will have the primary responsibility for: the scientific and
administrative leadership and coordination of the project at the awardee
institution. The PI will have primary responsibility for defining the
details for the projects within the guidelines of this FOA, and for performing
all scientific activities. The awardee institution will agree to accept
the close coordination, cooperation, and participation of the NIH staff (NIH
Roadmap Officials, PROMIS Scientists, NIH Science Officers, NIH Chief Science
Officer, and the NIH Project Officer) in those aspects of scientific and
technical management of the project as described below.

2.
Provide goals for procedures and protocols, quality, and cost to the NIH
Project Officer and Chief Science Officer as requested (usually at the outset
of the award and in six-month progress reports, but also at other times as
requested by the Project Officer and Chief Science Officer).

3.
Serve on the PROMIS Steering Committee, and participate, along with critical
staff, in the PROMIS Steering Committee meetings held four times annually,
three times /year in the metropolitan Washington, DC area.

4.
Adhere to PROMIS guidelines and other policies that might be established, as
agreed upon by the PNSC, PNEC and Chief Science Officer, e.g., regarding data
release, IP, and/or publications and the sharing of research resources, tools,
and data of interest with other PROMIS sites and centers, e.g., regarding data
release, IP, and/or publications and the sharing of research resources, tools,
and data of interest with other PROMIS sites and centers, to the extent consistent with the applicant’s submitted
statements and applicable grant regulations.

5.
Ensure, if consistent with the applicant’s submitted statements and
applicable grant regulations, that primary and secondary data, protocols and
procedures are made available to meet the goals of the program, (e.g. deposited
in a centralized public database, as specified by the NIH Project Officer and
NIH Science Officers) according to a timeline agreed upon by the PNSC and the
PNEC, and to the extent consistent with the applicant’s submitted
statements and applicable grant regulations, assure that resources developed as
a part of this project (e.g., procedures and protocols) are made publicly
available according to guidelines determined by the PNSC and PNEC consistent
with achieving the goals of the program.

6. Accept and implement
all scientific, practical, and policy decisions approved by the PNSC to
the extent consistent with the applicant’s submitted statements and
applicable grant regulations.

7. Submit data for
quality assessment in any reasonable manner specified by the PNSC.

8. Submit periodic
(e.g., six-month and annual) progress reports in a standard format, as
reasonably agreed upon by the PNSC and PNEC.

9. Agree not to disclose confidential
information obtained from other members of the PROMIS network.

10. Be prepared for annual administrative
site visits by NIH staff.

11. Be solely
responsible for the timely acquisition of all appropriate proprietary rights,
including intellectual property rights, and all materials needed for the
awardee to perform the project.

12. Be required
to report to the U.S. Government all inventions made in the performance of the
project, as specified by 35 U.S.C. Sec. 200-212 (Bayh-Dole Act).

Before, during, and subsequent to the award, the U.S.
Government is not required to obtain for the awardee any proprietary rights,
including intellectual property rights, or any materials needed by the awardee
to perform the project.

Awardees are expected to make new information and materials
known to the research community in a timely manner through publications, web
announcements, and reports to the PROMIS staff, or other mechanisms.

Awardees
will retain custody of and have primary rights to the data and software
developed under these awards, subject to Government rights of access consistent
with current HHS, PHS, and NIH policies.

2.
A.2. NIH Responsibilities

The
NIH PROMIS Chief Science Officer, Science Officers, and Project Officer will
have substantial programmatic involvement that is above and beyond the normal
stewardship role in awards, as described below.

PROMIS
ChiefScience
Officer (CSO) Responsibilities: The PROMIS Chief Science Officer is
an NIH extramural program scientist who will have substantial scientific
involvement during the conduct of this activity, through technical assistance,
advice, and coordination above and beyond normal program stewardship for
grants. This includes facilitating the partnership relationship between NIH and
the PROMIS PNC, PTC and PSC, helping to maintain the overall scientific balance
in the program commensurate with new research and emerging research
opportunities, and ensuring that the activities of the PROMIS sites are
consistent with the mission of the NIH. However, the role of the Chief Science
Officer will be to facilitate and not to direct. Each PROMIS site will have one
designated NIH Science Officer and a given Science Officer may be assigned to
multiple centers.

The
PROMIS Chief Science Officer (CSO) will have the following substantial involvement:

1) Provide relevant
scientific expertise and overall knowledge.

2) Assist in the
integration of the individual PROMIS sites and centers into a research network,
including coordinating regular conference calls for sharing of approaches and
fostering inter-center collaborations.

3) Participate, as a
voting member, with the other PROMIS Steering Committee members in the group
process of setting research priorities and milestones, deciding optimal
research approaches and protocol designs, and contributing to the adjustment of
research protocols or approaches as necessary. The Chief Science Officer will
assist and facilitate the group process and not direct it.

4) Serve as scientific
liaison between the awardees, other NIH program staff, and the PROMIS Science
Officers.

5) Assist in avoiding unnecessary duplication
of effort across the PROMIS, and help coordinate collaborative research efforts
that involve multiple sites.

6) Review and comment on critical stages of
PROMIS development for presentation to the PROMIS Science Officers and Project
Team.

7) Retain the option to recommend, with the
advice of the Science Officers, re-allocation of NIH support among awardees, as
scientific goals evolve.

8) Consult with non-NIH experts in the field as
necessary and appropriate.

3) Serve as subject
matter experts to assist other NIH program staff in providing advice to
investigators about the PROMIS program.

4) Assist the Chief
Science Officer in reviewing critical stages of development in the research
program for presentation to the NIH Project Team and to make determinations
regarding the implementation of subsequent stages.

5) Facilitate
interactions between the awardee institution and investigators at other
institutions.

6) Provide information
about ongoing NIH-supported research and resources, and recommend the
development of PROMIS related initiatives to the Project Team (see below).

7) Participate with the
other PROMIS Steering Committee members in the group process of setting
research priorities and milestones, deciding optimal research approaches and
protocol designs, and contributing to the adjustment of research protocols or
approaches as necessary and appropriate in a voting liaison member role.

8) Be a voting member of the PROMIS Steering
Committee

Project
Officer Responsibilities: The Project
Officer is an NIH program staff member who will have responsibility for normal
program oversight and stewardship of the PROMIS Network on behalf of the PROMIS
Project team.

The
Project Officer will
have the following involvement:

1)
Approval of progress reports and support for out-years, on behalf of the NIH
for the U01 and U54 cooperative agreements that comprise the PROMIS network.

2)
Have the option to recommend, following consultation with the Chief Science
Officer, PROMIS Science Officers and NIH officials, the possible withholding,
reduction, or reallocation, as appropriate, of support from any center that
substantially fails to achieve its goals according to the milestones agreed to
by the center at the time of the award or fails to comply with the Terms and
Conditions of the award, at the appropriate times.

3)
Have the option to recommend, following consultation with the Chief Science
Officer and NIH Science Officers and the NIH officials, an increase in support
to engage in further research efforts under the program, as appropriate, for
any center showing that additional research would be substantially exceeding
its goals according to the milestones agreed to by the center and substantially
improving state-of-the-art capabilities, at the appropriate times.

5)
Carry out continuous review of all activities to ensure objectives are being
met.

PROMIS Project Team Responsibilities: The PROMIS Project
Team will serve as the trans-NIH body consulting and advising PROMIS
activities. PROMIS Project Team membership will include one or more
representative(s) from each of the NIH Institutes and Centers (IC)
participating in the PROMIS network.

The PROMIS Project Team may be involved in following
activities:

1)
Review and provide advice about current and future direction based on
recommendations from the Project Officer and the Chief Science Officer.

2)
Evaluate progress of the PROMIS projects in consultation with the Project
Officer, Chief Science Officer, and the PROMIS Science Officers.

Additionally, an agency program official or IC program
director will be responsible for the normal scientific and programmatic
stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities
(optional)

Refer to the Organizational Structure of the PROMIS
Network and Network Center and Governance of the PROMIS Network in
Section I, 2. Research Objectives.

Each
full member will have one vote. Awardee members of the Steering Committee will
be required to accept and implement policies approved by the Steering
Committee.

2.A.4.
Arbitration Process

Any disagreements that
may arise in scientific or programmatic matters (within the scope of the award)
between award recipients and the NIH may be brought to arbitration. An
Arbitration Panel composed of three members will be convened. It will have
three members: a designee of the Steering Committee chosen without NIH staff
voting, one NIH designee, and a third designee with expertise in the relevant
area who is chosen by the other two; in the case of individual disagreement,
the first member may be chosen by the individual awardee. This special
arbitration procedure in no way affects the awardee's right to appeal an
adverse action that is otherwise appealable in accordance with PHS regulations
42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

The
PD/PI(s) of each PROMIS Research Site will be responsible for organizing an
annual report on all of the activities of their site. The PD/PI(s) of each
PROMIS Research Site will be responsible for providing semi-annual status
reports to NIH and reports to the Steering Committee as agreed upon by the
Network.

A
final progress report, invention statement, and Financial Status Report are
required when an award is relinquished when a recipient changes institutions or
when an award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research, peer review, and financial or grants
management issues:

Human Subjects
Protection:Federal
regulations (45CFR46) require that applications and proposals involving human
subjects must be evaluated with reference to the risks to the subjects, the
adequacy of protection against these risks, the potential benefits of the research
to the subjects and others, and the importance of the knowledge gained or to be
gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should be
commensurate with risk. The establishment of data and safety monitoring boards
(DSMBs) is required for multi-site clinical trials involving interventions that
entail potential risks to the participants (NIH Policy for Data and Safety
Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing
Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators
should seek guidance from their institutions, on issues related to
institutional policies and local IRB rules, as well as local, State and Federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy
for Genome-Wide Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/

Access
to Research Data through the Freedom of Information Act:The Office of
Management and Budget (OMB) Circular A-110 has been revised to provide access
to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported
in whole or in part with Federal funds and (2) cited publicly and officially by
a Federal agency in support of an action that has the force and effect of law
(i.e., a regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has provided
guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Sharing of Model
Organisms:NIH is committed to
support efforts that encourage sharing of important research resources
including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the application/proposal
a description of a specific plan for sharing and distributing unique model
organism research resources generated using NIH funding or state why such
sharing is restricted or not possible. This will permit other researchers to
benefit from the resources developed with public funding. The inclusion of a
model organism sharing plan is not subject to a cost threshold in any year and
is expected to be included in all applications where the development of model
organisms is anticipated.

Inclusion of Women
And Minorities in Clinical Research:It is the policy of the
NIH that women and members of minority groups and their sub-populations must be
included in all NIH-supported clinical research projects unless a clear and
compelling justification is provided indicating that inclusion is inappropriate
with respect to the health of the subjects or the purpose of the research. This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43). All investigators proposing clinical research should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of
Children as Participants in Clinical Research:The NIH maintains a
policy that children (i.e., individuals under the age of 21) must be included
in all clinical research, conducted or supported by the NIH, unless there are
scientific and ethical reasons not to include them.

Required
Education on the Protection of Human Subject Participants:NIH policy requires
education on the protection of human subject participants for all investigators
submitting NIH applications for research involving human subjects and
individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem
Cells (hESC):Criteria for federal
funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy Requirement:In
accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly
available no later than 12 months after publication. As of May 27, 2008,
investigators must include the PubMed Central reference number when citing an
article in NIH applications, proposals, and progress reports that fall under
the policy, and was authored or co-authored by the investigator or arose from
the investigator’s NIH award. For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards
for Privacy of Individually Identifiable Health Information:The Department
of Health and Human Services (DHHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the DHHS
Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH
Grant Applications or Appendices:
All
applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or
Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for the review because reviewers are
under no obligation to view the Internet sites. Furthermore, we caution
reviewers that their anonymity may be compromised when they directly access an
Internet site.

Healthy
People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive
Order 12372. Awards are made under the authorization of Sections 301 and 405 of
the Public Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the
terms and conditions, cost principles, and other considerations described in
the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan
Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov.